Reactive oxygen (RO) has been identified as an important effector in ageing and lifespan determination. The specific cell types, however, in which oxidative damage acts to limit lifespan of the whole organism have not been explicitly identified. The association between mutations in the gene encoding the oxygen radical metabolizing enzyme CuZn superoxide dismutase (SOD1) and loss of motorneurons in the brain and spinal cord that occurs in the life-shortening paralytic disease, Familial Amyotrophic Lateral Sclerosis (FALS; ref.
BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS: We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families.
This article proposes that behavioural advancement during mammalian evolution had been in part mediated through extension of total developmental time. Such time extensions would have resulted in increased numbers of neuronal precursor cells, hence larger brains and a disproportionate increase in the neocortex. Larger neocortical areas enabled new connections to be formed during development and hence expansion of existing behavioural circuits.
Dampening of insulin/insulin-like growth factor-1 (IGF1) signaling results in the extension of lifespan in invertebrate as well as murine models. The impact of this evolutionarily conserved pathway on the modulation of human lifespan remains unclear. We previously identified two IGF1R mutations (Ala-37-Thr and Arg-407-His) that are enriched in Ashkenazi Jewish centenarians as compared to younger controls and are associated with the reduced activity of the IGF1 receptor as measured in immortalized lymphocytes.
With ageing, there is a loss of adult stem cell function. However, there is no direct evidence that this has a causal role in ageing-related decline. We tested this using muscle-derived stem/progenitor cells (MDSPCs) in a murine progeria model. Here we show that MDSPCs from old and progeroid mice are defective in proliferation and multilineage differentiation. Intraperitoneal administration of MDSPCs, isolated from young wild-type mice, to progeroid mice confer significant lifespan and healthspan extension.
DNA methylation patterns change as individuals grow older, and DNA methylation appears susceptible to modification by the diet. Thus DNA methylation may be a mechanism through which diet can affect aging and longevity. We propose that effects on DNA methylation also contribute to the extension in lifespan observed in response to dietary restriction. Relationships between diet-induced changes in DNA methylation and parallel effects on aging and/or lifespan could, of course, be purely associative.
How we age as individuals is no doubt a complex interaction of genetic and environmental factors. Studies of certain populations with optimal environments and health-related behaviors, as well as twin studies, suggest that the average set of genetic variations should facilitate the average person's ability to live to around age 85. Average life expectancies are lower than this because we generally fight survival advantage with bad health habits that can lead to premature aging, chronic illness, and death at a significantly younger age.
The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry
OBJECTIVE: A systematic genome survey was initiated to identify loci that affect the likelihood of reaching age 90 with preserved cognition. This communication describes the clinical characterization and comparison of the experimental groups, validation of the experimental method, and results for the Y chromosome. METHODS: The genome survey was conducted at 10 cM resolution for simple sequence tandem repeat polymorphisms (SSTRPs) that identify genes for successful aging by virtue of linkage disequilibrium.
JAMA: the journal of the American Medical Association
CONTEXT: Individuals with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. OBJECTIVE: To identify specific biological and genetic factors that are associated with or reliably define a human longevity phenotype.